Direct chlorination of the methyl group on an aromatic or N-heteroaromatic compound presents problems when the compound contains other substituents such as alkoxy, alkyl or alkoxy or alkyl substituted aryl groups in addition to the methyl group to be chlorinated. In the above cases, direct chlorination of the methyl group would also result in chlorination of the substituent groups.
To solve the above problem, processes have been developed for obtaining a halogenated methyl group, particularly a trichloromethyl group, by treating a carboxylic acid group with phosphorus pentachloride, usually in the presence of excess thionyl chloride. Examples of these processes can be found at Chemical Abstracts 74, 125566y, Chemical Abstracts 79, 31986m and Chemical Abstracts 81, 105395h. The methods disclosed in the above references are specific for the conversion of a carboxylic acid group adjacent, or alpha, to the heteroatom of a N-heteroaromatic (N=nitrogen) compound.
A non-specific method for converting a carboxylic acid group to a trichloromethyl group is disclosed in U.S. Pat. No. 4,419,514. The method disclosed in the above patent uses a phenylphosphonic dichloride and phosphorus pentachloride. The above method suffers from the disadvantage of requiring the handling of solid phosphorus pentachloride which, due to its sensitivity to moisture, requires special handling conditions.
U.S. Pat. No. 4,249,009 discloses a process for the preparation of 2-chloro-5-trifluoromethylpyridine wherein 5-carboxy-2-hydroxypyridine is treated with a chlorinating agent and a fluorinating agent. The preferred chlorinating agent is phosphorus pentachloride and the inventors disclose that the reaction proceeds through an acid chloride intermediate. The above patent does not teach the formation of the trichloromethyl compound.
U.S. Pat. No. 4,167,525 discloses a process for the preparation of an aromatic acyl chloride. In the above patent, an aromatic carboxylic acid is first treated with phosphorus trichloride and chlorine. The phosphorus pentachloride by-product is treated with a reagent prepared from partially hydrolyzed phosphorus compounds to convert the phosphorus pentachloride to phosphorus oxychloride and the phosphorus oxychloride is removed by distillation. The above method suffers from the disadvantage of requiring additional phosphorus compounds to convert the phosphorus pentachloride to phosphorus oxychloride.